5-177600183-G-T

Position:

• chr5-177600183-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007255.3(B4GALT7):​c.-28G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,331,954 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (26 hom.)
• Consequence: B4GALT7 NM_007255.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.193

Genes affected

B4GALT7 (HGNC:930): (beta-1,4-galactosyltransferase 7) This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]

B4GALT7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-177600183-G-T is Benign according to our data. Variant chr5-177600183-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 506362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00202 (307/151742) while in subpopulation SAS AF= 0.0203 (98/4826). AF 95% confidence interval is 0.0171. There are 1 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT7	NM_007255.3	c.-28G>T		5_prime_UTR_variant	1/6	ENST00000029410.10	NP_009186.1
B4GALT7	XM_047416681.1	c.-1138G>T		5_prime_UTR_variant	1/7		XP_047272637.1
B4GALT7	XM_047416682.1	c.-423G>T		5_prime_UTR_variant	1/7		XP_047272638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT7	ENST00000029410	c.-28G>T		5_prime_UTR_variant	1/6	1	NM_007255.3	ENSP00000029410.5

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 306 AN: 151634 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000854

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.000863

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00252

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00513 AC: 206 AN: 40194 Hom.: 3 AF XY: 0.00692 AC XY: 167 AN XY: 24136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00246 AC: 2900 AN: 1180212 Hom.: 26 Cov.: 30 AF XY: 0.00274 AC XY: 1576 AN XY: 574566

Gnomad4 AFR exome AF: 0.000207

Gnomad4 AMR exome AF: 0.000549

Gnomad4 ASJ exome AF: 0.000276

Gnomad4 EAS exome AF: 0.000262

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.00190

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00202 AC: 307 AN: 151742 Hom.: 1 Cov.: 31 AF XY: 0.00224 AC XY: 166 AN XY: 74158

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000853

Gnomad4 ASJ AF: 0.000867

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.000863

Gnomad4 NFE AF: 0.00252

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.000956 Hom.: 0

Bravo AF: 0.00149

Asia WGS AF: 0.00348 AC: 12 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 15, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs562627459; hg19: chr5-177027184;